title: Extension of life-span by introduction of telomerase into normal human cells.
abstract: Normal human cells undergo a finite number of cell divisions and ultimately enter a nondividing state called replicative senescence. It has been proposed that telomere shortening is the molecular clock that triggers senescence. To test this hypothesis, two telomerase-negative normal human cell types, retinal pigment epithelial cells and foreskin fibroblasts, were transfected with vectors encoding the human telomerase catalytic subunit. In contrast to telomerase-negative control clones, which exhibited telomere shortening and senescence, telomerase-expressing clones had elongated telomeres, divided vigorously, and showed reduced straining for beta-galactosidase, a biomarker for senescence. Notably, the telomerase-expressing clones have a normal karyotype and have already exceeded their normal life-span by at least 20 doublings, thus establishing a causal relationship between telomere shortening and in vitro cellular senescence. The ability to maintain normal human cells in a phenotypically youthful state could have important applications in research and medicine.
authors.affiliation: Geron Corporation, Menlo Park, CA 94025, USA.
authors.forename: A G
authors.initials: AG
authors.lastname: Bodnar
authors.forename: M
authors.initials: M
authors.lastname: Ouellette
authors.forename: M
authors.initials: M
authors.lastname: Frolkis
authors.forename: S E
authors.initials: SE
authors.lastname: Holt
authors.forename: C P
authors.initials: CP
authors.lastname: Chiu
authors.forename: G B
authors.initials: GB
authors.lastname: Morin
authors.forename: C B
authors.initials: CB
authors.lastname: Harley
authors.forename: J W
authors.initials: JW
authors.lastname: Shay
authors.forename: S
authors.initials: S
authors.lastname: Lichtsteiner
authors.forename: W E
authors.initials: WE
authors.lastname: Wright
mesh_terms: D015415:Biomarkers; D002384:Catalysis; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D016922:Cellular Senescence; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins; D005347:Fibroblasts / Q000166:cytology; D006706:Homeostasis; D006801:Humans; D007621:Karyotyping; D010641:Phenotype; D010857:Pigment Epithelium of Eye / Q000166:cytology; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012313:RNA; D012194:RNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000201:enzymology; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D014162:Transfection; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D015415:Biomarkers; D004268:DNA-Binding Proteins; D011506:Proteins; C422952:telomerase RNA; D012313:RNA; D012194:RNA-Directed DNA Polymerase; D019098:Telomerase; D001616:beta-Galactosidase